# US 7,745,118 B2 · Comparative genomic resequencing

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- Number: US 7,745,118 B2
- Document ID: US7745118B2
- Status: Granted
- Kind: B2
- Application number: 11/101,841
- Filed: 2005-04-08
- Published: 2005-11-24
- Granted: 2010-06-29
- Earliest claimed: 2004-04-08
- Assignees: Roche Nimblegen, Inc.
- Inventors: Roland D Green; Steve Smith; Thomas Albert; Emile F. Nuwaysir
- Web page: https://patentgrep.com/patent/US7745118B2

## CPC

- C12Q 1/689: for bacteria
- C12Q 1/6827: for detection of mutation or polymorphism
- C12Q 1/6837: using probe arrays or probe chips (C12Q1/6874 takes precedence)
- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- C12Q 1/6869: Methods for sequencing
- C12Q 2600/156: Polymorphic or mutational markers
- Y10S 977/791: Molecular array
- Y10S 977/795: Composed of biological material
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present invention is an improved method of resequencing DNA using microarrays to rapidly map and identify SNPs, deletions and amplification events present in the genome of an organism. The method is performed by hybridizing a reference and a test genome to two separate arrays with each array exhibiting a specific intensity pattern. The intensity differences between the reference and the test genome arrays are used to produce a mutation map. The mapped differences are resequenced on a set of resequencing arrays to identify specific genetic mutations.

## Claims

### Claim 1

A method for identifying genetic mutations in a test genome of an organism relative to a reference genome of the an organism, the method comprising the steps of:
a) hybridizing the reference genome and the test genome in separate hybridization reactions to a genomic tiling array that comprises a plurality of probes that tile the reference genome across a plurality of regions having a stagger of more than one nucleotide to produce a reference intensity pattern and a test intensity pattern;
b) identifying in the plurality of regions a subset of regions of possible genetic mutation in the test genome in which the test intensity pattern differs from the reference intensity pattern; and
c) resequencing the subset of regions of possible genetic mutation in the test genome on a resequencing array.

### Claim 2 (depends on 1)

The method of claim 1 wherein the test genome is haploid.

### Claim 3 (depends on 1)

The method of claim 1 wherein the test genome is a Salmonella enterica ty21a genome.

### Claim 4 (depends on 1)

The method of claim 1 wherein the test genome is a haploid preparation of a diploid genome.

### Claim 5 (depends on 1)

The method of claim 1 wherein the regions that span more than one nucleotide tile the reference genome with a stagger of seven nucleotides.

### Claim 6 (depends on 1)

The method of claim 1 wherein the resequencing array includes a probe for each possible nucleotide at each nucleotide position in each region in the subset.

### Claim 7 (depends on 1)

The method of claim 1 wherein the genetic mutation is a single nucleotide polymorphism.

### Claim 8 (depends on 1)

The method of claim 1 wherein the genetic mutation is an insertion.

### Claim 9 (depends on 1)

The method of claim 1 wherein the genetic mutation is a deletion.

### Claim 10 (depends on 1)

The method of claim 1 wherein the genetic mutation is an inversion.